Top

BMC Anesthesiology

Published in:

Open Access 01-12-2018 | Research article

Effects of prebiotic galacto-oligosaccharide on postoperative cognitive dysfunction and neuroinflammation through targeting of the gut-brain axis

Authors: Xu-Dong Yang, Li-Kuan Wang, Hai-Yin Wu, Liang Jiao

Published in: BMC Anesthesiology | Issue 1/2018

Abstract

Background

Surgery-induced neuroinflammation plays an important role in postoperative cognitive dysfunction (POCD). Gut microbiota is a key regulator of neurological inflammation. Nurturing with prebiotics is an effective microbiota manipulation that can regulate host immunity and cognition. The aim of the present study was to test whether administration of the prebiotic Bimuno® (galactooligosaccharide (B-GOS) mixture) could ameliorate POCD and attenuate surgery-induced neuroinflammation through the microbiota-brain-axis.

Methods

Adult rats undergoing abdominal surgery under isoflurane anesthesia were fed with water or prebiotic B-GOS supplementation (15 g/L) for 3 weeks. Novel objective recognition task was employed for testing cognitive changes on postoperative day three. Expression of microglial marker Iba-1 in the hippocampus was assessed by immunohistochemical staining. Expression levels of phenotypic gene markers of activated microglia (M1: iNOS, CD68, CD32; M2: Ym1, CD206, and SOCS3) in hippocampus were determined by quantitative polymerase chain reaction (qPCR). Inflammatory cytokines in the hippocampus were assessed using enzyme-linked immunosorbent assay (ELISA). Feces were collected for microbial community analysis.

Results

Rats exhibited an impairment in novel objective recognition 3 days after surgery compared with control rats (P < .01). In the hippocampus, expressions of Iba-1 and M1 markers of surgical rats were significantly upregulated. Similarly, expressions of SOCS3 and CD206 in the hippocampus were upregulated. Additionally, increasing levels of IL-6 and IL-4 were evident in the hippocampus. Administration of B-GOS significantly alleviated cognitive decline induced by surgery (P < .01). B-GOS-fed rats showed a significantly downregulated activation of microglia and expressions of M1-related genes and SOCS3 and IL-6. While there was no significant difference in expressions of CD206 and Ym1 and IL-4 between the surgical and B-GOS groups. Analysis of gut microbiome found that administration of B-GOS induced a significant change beta diversity of the gut microbiome and proliferation of Bifidobacterium and other potentially anti-inflammatory microbes.

Conclusions

Administration of B-GOS has a beneficial effect on regulating neuroinflammatory and cognitive impairment in a rat model of abdominal surgery and was associated with the manipulation of gut microbiota.

Needham MJ, Webb CE, Bryden DC. Postoperative cognitive dysfunction and dementia: what we need to know and do. Br J Anaesth. 2017;119:i115–i25.CrossRef

Evered L, Scott DA, Silbert B, Maruff P. Postoperative cognitive dysfunction is independent of type of surgery and anesthetic. Anesth Analg. 2011;112:1179–85.CrossRef

Krenk L, Rasmussen LS, Kehlet H. New insights into the pathophysiology of postoperative cognitive dysfunction. Acta Anaesthesiol Scand. 2010;54:951–6.CrossRef

Riedel B, Browne K, Silbert B. Cerebral protection: inflammation, endothelial dysfunction, and postoperative cognitive dysfunction. Curr Opin Anaesthesiol. 2014;27:89–97.CrossRef

Dheen ST, Kaur C, Ling EA. Microglial activation and its implications in the brain diseases. Curr Med Chem. 2007;14:1189–97.CrossRef

Hovens IB, Schoemaker RG, van der Zee EA, Absalom AR, Heineman E, van Leeuwen BL. Postoperative cognitive dysfunction: involvement of neuroinflammation and neuronal functioning. Brain Behav Immun. 2014;38:202–10.CrossRef

Hovens IB, van Leeuwen BL, Nyakas C, Heineman E, van der Zee EA, Schoemaker RG. Postoperative cognitive dysfunction and microglial activation in associated brain regions in old rats. Neurobiol Learn Mem. 2015;118:74–9.CrossRef

Eggen BJ, Raj D, Hanisch UK, Boddeke HW. Microglial phenotype and adaptation. J NeuroImmune Pharmacol. 2013;8:807–23.CrossRef

Hu X, Leak RK, Shi Y, Suenaga J, Gao Y, Zheng P, et al. Microglial and macrophage polarization-new prospects for brain repair. Nat Rev Neurol. 2015;11:56–64.CrossRef

10.

Lee JH, Kam EH, Kim SY, Cheon SY, Kim EJ, Chung S, et al. Erythropoietin attenuates postoperative cognitive dysfunction by shifting macrophage activation toward the M2 phenotype. Front Pharmacol. 2017;8:839.CrossRef

11.

Wang HL, Liu H, Xue ZG, Liao QW, Fang H. Minocycline attenuates post-operative cognitive impairment in aged mice by inhibiting microglia activation. J Cell Mol Med. 2016;20:1632–9.CrossRef

12.

Smith PA. The tantalizing links between gut microbes and the brain. Nature. 2015;526:312–4.CrossRef

13.

Erny D, Prinz M. Microbiology: gut microbes augment neurodegeneration. Nature. 2017;544:304–5.CrossRef

14.

Kamada N, Seo SU, Chen GY, Nunez G. Role of the gut microbiota in immunity and inflammatory disease. Nat Rev Immunol. 2013;13:321–35.CrossRef

15.

Tremlett H, Bauer KC, Appel-Cresswell S, Finlay BB, Waubant E. The gut microbiome in human neurological disease: a review. Ann Neurol. 2017;81:369–82.CrossRef

16.

Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, et al. Expert consensus document: the international scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. 2017;14:491–502.PubMed

17.

Chunchai T, Thunapong W, Yasom S, Wanchai K, Eaimworawuthikul S, Metzler G, et al. Decreased microglial activation through gut-brain axis by prebiotics, probiotics, or synbiotics effectively restored cognitive function in obese-insulin resistant rats. J Neuroinflammation. 2018;15:11.CrossRef

18.

Pistollato F, Sumalla Cano S, Elio I, Masias Vergara M, Giampieri F, Battino M. Role of gut microbiota and nutrients in amyloid formation and pathogenesis of Alzheimer disease. Nutr Rev. 2016;74:624–34.CrossRef

19.

Vulevic J, Drakoularakou A, Yaqoob P, Tzortzis G, Gibson GR. Modulation of the fecal microflora profile and immune function by a novel trans-galactooligosaccharide mixture (B-GOS) in healthy elderly volunteers. Am J Clin Nutr. 2008;88:1438–46.PubMed

20.

Williams S, Chen L, Savignac HM, Tzortzis G, Anthony DC, Burnet PW. Neonatal prebiotic (BGOS) supplementation increases the levels of synaptophysin, GluN2A-subunits and BDNF proteins in the adult rat hippocampus. Synapse. 2016;70:121–4.CrossRef

21.

Savignac HM, Couch Y, Stratford M, Bannerman DM, Tzortzis G, Anthony DC, et al. Prebiotic administration normalizes lipopolysaccharide (LPS)-induced anxiety and cortical 5-HT2A receptor and IL1-beta levels in male mice. Brain Behav Immun. 2016;52:120–31.CrossRef

22.

Hovens IB, Schoemaker RG, van der Zee EA, Heineman E, Nyakas C, van Leeuwen BL. Surgery-induced behavioral changes in aged rats. Exp Gerontol. 2013;48:1204–11.CrossRef

23.

Rosczyk HA, Sparkman NL, Johnson RW. Neuroinflammation and cognitive function in aged mice following minor surgery. Exp Gerontol. 2008;43:840–6.CrossRef

24.

Hovens IB, van Leeuwen BL, Mariani MA, Kraneveld AD, Schoemaker RG. Postoperative cognitive dysfunction and neuroinflammation; cardiac surgery and abdominal surgery are not the same. Brain Behav Immun. 2016;54:178–93.CrossRef

25.

Tian XS, Tong YW, Li ZQ, Li LX, Zhang T, Ren TY, et al. Surgical stress induces brain-derived neurotrophic factor reduction and postoperative cognitive dysfunction via glucocorticoid receptor phosphorylation in aged mice. CNS Neurosci Ther. 2015;21:398–409.CrossRef

26.

Savage S, Ma DIII. Animal behaviour testing: memory. Br J Anaesth. 2014;113:6–9.CrossRef

27.

Cibelli M, Fidalgo AR, Terrando N, Ma D, Monaco C, Feldmann M, et al. Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol. 2010;68:360–8.CrossRef

28.

Terrando N, Eriksson LI, Ryu JK, Yang T, Monaco C, Feldmann M, et al. Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol. 2011;70:986–95.CrossRef

29.

Wan Y, Xu J, Ma D, Zeng Y, Cibelli M, Maze M. Postoperative impairment of cognitive function in rats: a possible role for cytokine-mediated inflammation in the hippocampus. Anesthesiology. 2007;106:436–43.CrossRef

30.

Hovens IB, Schoemaker RG, van der Zee EA, Heineman E, Izaks GJ, van Leeuwen BL. Thinking through postoperative cognitive dysfunction: how to bridge the gap between clinical and pre-clinical perspectives. Brain Behav Immun. 2012;26:1169–79.CrossRef

31.

Dorrestein PC, Mazmanian SK, Knight R. Finding the missing links among metabolites, microbes, and the host. Immunity. 2014;40:824–32.CrossRef

32.

Braniste V, Al-Asmakh M, Kowal C, Anuar F, Abbaspour A, Toth M, et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med. 2014;6:263ra158.CrossRef

33.

Erny D, Hrabe de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015;18:965–77.CrossRef

34.

Burokas A, Arboleya S, Moloney RD, Peterson VL, Murphy K, Clarke G, et al. Targeting the microbiota-gut-brain Axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol Psychiatry. 2017;82:472–87.CrossRef

35.

Chen D, Yang X, Yang J, Lai G, Yong T, Tang X, et al. Prebiotic effect of Fructooligosaccharides from Morinda officinalis on Alzheimer's disease in rodent models by targeting the microbiota-gut-brain Axis. Front Aging Neurosci. 2017;9:403.CrossRef

36.

Zhang X, Dong H, Li N, Zhang S, Sun J, Zhang S, et al. Activated brain mast cells contribute to postoperative cognitive dysfunction by evoking microglia activation and neuronal apoptosis. J Neuroinflammation. 2016;13:127.CrossRef

37.

Jiang P, Ling Q, Liu H, Tu W. Intracisternal administration of an interleukin-6 receptor antagonist attenuates surgery-induced cognitive impairment by inhibition of neuroinflammatory responses in aged rats. Exp Ther Med. 2015;9:982–6.CrossRef

38.

Azizi G, Mirshafiey A. The potential role of proinflammatory and antiinflammatory cytokines in Alzheimer disease pathogenesis. Immunopharmacol Immunotoxicol. 2012;34:881–95.CrossRef

39.

Croker BA, Krebs DL, Zhang JG, Wormald S, Willson TA, Stanley EG, et al. SOCS3 negatively regulates IL-6 signaling in vivo. Nat Immunol. 2003;4:540–5.CrossRef

40.

Chhor V, Le Charpentier T, Lebon S, Ore MV, Celador IL, Josserand J, et al. Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro. Brain Behav Immun. 2013;32:70–85.CrossRef

41.

Li Z, Liu F, Ma H, White PF, Yumul R, Jiang Y, et al. Age exacerbates surgery-induced cognitive impairment and neuroinflammation in Sprague-Dawley rats: the role of IL-4. Brain Res. 2017;1665:65–73.CrossRef

42.

Desbonnet L, Garrett L, Clarke G, Kiely B, Cryan JF, Dinan TG. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience. 2010;170:1179–88.CrossRef

43.

Kobayashi Y, Sugahara H, Shimada K, Mitsuyama E, Kuhara T, Yasuoka A, et al. Therapeutic potential of Bifidobacterium breve strain A1 for preventing cognitive impairment in Alzheimer's disease. Sci Rep. 2017;7:13510.CrossRef

44.

Gronier B, Savignac HM, Di Miceli M, Idriss SM, Tzortzis G, Anthony D, et al. Increased cortical neuronal responses to NMDA and improved attentional set-shifting performance in rats following prebiotic (B-GOS((R))) ingestion. Eur Neuropsychopharmacol. 2018;28:211–24.CrossRef

45.

Silk DB, Davis A, Vulevic J, Tzortzis G, Gibson GR. Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome. Aliment Pharmacol Ther. 2009;29:508–18.CrossRef

46.

Tzortzis G, Goulas AK, Gee JM, Gibson GR. A novel galactooligosaccharide mixture increases the bifidobacterial population numbers in a continuous in vitro fermentation system and in the proximal colonic contents of pigs in vivo. J Nutr. 2005;135:1726–31.CrossRef

47.

Jeong JJ, Woo JY, Kim KA, Han MJ, Kim DH. Lactobacillus pentosus var. plantarum C29 ameliorates age-dependent memory impairment in Fischer 344 rats. Lett Appl Microbiol. 2015;60:307–14.CrossRef

48.

Jung IH, Jung MA, Kim EJ, Han MJ, Kim DH. Lactobacillus pentosus var. plantarum C29 protects scopolamine-induced memory deficit in mice. J Appl Microbiol. 2012;113:1498–506.CrossRef

49.

Beilharz JE, Kaakoush NO, Maniam J, Morris MJ. The effect of short-term exposure to energy-matched diets enriched in fat or sugar on memory, gut microbiota and markers of brain inflammation and plasticity. Brain Behav Immun. 2016;57:304–13.CrossRef

50.

Sun L, Dong R, Xu X, Yang X, Peng M. Activation of cannabinoid receptor type 2 attenuates surgery-induced cognitive impairment in mice through anti-inflammatory activity. J Neuroinflammation. 2017;14:138.CrossRef

51.

Terrando N, Monaco C, Ma D, Foxwell BM, Feldmann M, Maze M. Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci U S A. 2010;107:20518–22.CrossRef

52.

Cohen SJ, Stackman RW, Jr. Assessing rodent hippocampal involvement in the novel object recognition task. A review. Behav Brain Res 2015;285:105–117.

53.

Hager AM, Dringenberg HC. Training-induced plasticity in the visual cortex of adult rats following visual discrimination learning. Learn Mem. 2010;17:394–401.CrossRef

54.

Sears RM, Schiff HC, LeDoux JE. Molecular mechanisms of threat learning in the lateral nucleus of the amygdala. Prog Mol Biol Transl Sci. 2014;122:263–304.CrossRef

Title: Effects of prebiotic galacto-oligosaccharide on postoperative cognitive dysfunction and neuroinflammation through targeting of the gut-brain axis
Authors: Xu-Dong Yang
Li-Kuan Wang
Hai-Yin Wu
Liang Jiao
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: BMC Anesthesiology / Issue 1/2018
Electronic ISSN: 1471-2253
DOI: https://doi.org/10.1186/s12871-018-0642-1

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Effects of prebiotic galacto-oligosaccharide on postoperative cognitive dysfunction and neuroinflammation through targeting of the gut-brain axis

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2018

Ultrasound-guided phrenic nerve block for intraoperative persistent hiccups: a case report

Survey of anesthesiologists’ practices related to steep Trendelenburg positioning in the USA

Does fentanyl or remifentanil provide better postoperative recovery after laparoscopic surgery? a randomized controlled trial

In vitro effects of levosimendan on muscle of malignant hyperthermia susceptible and non-susceptible swine

Gender differences in career development awards in United States’ anesthesiology and surgery departments, 2006–2016

Effect of single-dose dexmedetomidine on postoperative recovery after ambulatory ureteroscopy and ureteric stenting: a double blind randomized controlled study